Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
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Publication date
2015-11
Authors
Kato, Norihiro
Loh, Marie
Takeuchi, Fumihiko
Verweij, Niek
Wang, Xu
Zhang, Weihua
Kelly, Tanika N.
Saleheen, Danish
Lehne, Benjamin
Leach, Irene Mateo
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Article
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taverne
Abstract
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 x 10(-11) to 5.0 x 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 x 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
Keywords
PULMONARY ARTERIAL-HYPERTENSION, CENTRIC ARRAY, RISK-FACTORS, CARDIOVASCULAR-DISEASE, VARIANTS, REGIONS, KIDNEY, TISSUE, METAANALYSIS, INDIVIDUALS, Taverne, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.
Citation
Kato, N, Loh, M, Takeuchi, F, Verweij, N, Wang, X, Zhang, W, Kelly, T N, Saleheen, D, Lehne, B, Leach, I M, Drong, A W, Abbott, J, Wahl, S, Tan, S-T, Scott, W R, Campanella, G, Chadeau-Hyam, M, Afzal, U, Ahluwalia, T S, Bonder, M J, Chen, P, Dehghan, A, Edwards, T L, Esko, T, Go, M J, Harris, S E, Hartiala, J, Kasela, S, Kasturiratne, A, Khor, C-C, Kleber, M E, Li, H, Mok, Z Y, Nakatochi, M, Sapari, N S, Saxena, R, Stewart, A F R, Stolk, L, Tabara, Y, Teh, A L, Wu, Y, Wu, J-Y, Zhang, Y, Aits, I, Alves, A D S C, Das, S, Tragante, V, Doevendans, P A, Spiering, W, Asselbergs, F W, BIOS Consortium, CARDIo GRAMplusCD, LifeLines Cohort Study & InterAct Consortium 2015, 'Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation', Nature Genetics, vol. 47, no. 11, pp. 1282–1293. https://doi.org/10.1038/ng.3405